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Genetics Home Reference: your guide to understanding genetic conditions
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FXN

Reviewed May 2010

What is the official name of the FXN gene?

The official name of this gene is “frataxin.”

FXN is the gene's official symbol. The FXN gene is also known by other names, listed below.

What is the normal function of the FXN gene?

The FXN gene provides instructions for making a protein called frataxin. This protein is found in cells throughout the body, with the highest levels in the heart, spinal cord, liver, pancreas, and muscles used for voluntary movement (skeletal muscles). Within cells, frataxin is found in energy-producing structures called mitochondria. Although its function is not fully understood, frataxin appears to help assemble clusters of iron and sulfur molecules that are critical for the function of many proteins, including those needed for energy production.

One region of the FXN gene contains a segment of DNA known as a GAA trinucleotide repeat. This segment is made up of a series of three DNA building blocks (one guanine and two adenines) that appear multiple times in a row. In most people, the number of GAA repeats in the FXN gene is fewer than 12 (referred to as short normal). Sometimes, however, the GAA segment is repeated 12 to 33 times (referred to as long normal).

How are changes in the FXN gene related to health conditions?

Friedreich ataxia - caused by mutations in the FXN gene

Friedreich ataxia results from an increased number of copies (expansion) of the GAA trinucleotide repeat in the FXN gene. In people with this condition, the GAA segment is abnormally repeated 66 to more than 1,000 times. The length of the GAA trinucleotide repeat appears to be related to the age at which the symptoms of Friedreich ataxia appear. People with GAA segments repeated fewer than 300 times tend to have a later appearance of symptoms (after age 25) than those with larger GAA trinucleotide repeats.

Most individuals with Friedreich ataxia have the expanded GAA trinucleotide repeat in both copies of the FXN gene. About 2 percent of people with this condition have an expanded GAA trinucleotide repeat in one copy of the FXN gene and a different kind of mutation in the other copy of the gene. In most of these cases, the other mutation changes a single DNA building block (nucleotide) within the FXN gene.

It is not fully understood how FXN gene mutations cause Friedreich ataxia. Mutations in this gene disrupt production of frataxin, greatly reducing the amount of this protein in cells. A shortage of frataxin appears to decrease the activity of proteins that contain iron-sulfur clusters, which could impair the production of energy in mitochondria. Cells with insufficient amounts of frataxin are also particularly sensitive to reactive molecules (free radicals) that can damage and destroy cells. Cells in the brain, spinal cord, and muscles that are damaged or have inadequate energy supplies may not function properly, leading to the signs and symptoms of Friedreich ataxia.

Where is the FXN gene located?

Cytogenetic Location: 9q21.11

Molecular Location on chromosome 9: base pairs 69,035,562 to 69,100,177

The FXN gene is located on the long (q) arm of chromosome 9 at position 21.11.

The FXN gene is located on the long (q) arm of chromosome 9 at position 21.11.

More precisely, the FXN gene is located from base pair 69,035,562 to base pair 69,100,177 on chromosome 9.

See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.

Where can I find additional information about FXN?

You and your healthcare professional may find the following resources about FXN helpful.

You may also be interested in these resources, which are designed for genetics professionals and researchers.

What other names do people use for the FXN gene or gene products?

  • CyaY
  • FA
  • FARR
  • FRDA
  • FRDA_HUMAN
  • Friedreich ataxia
  • MGC57199
  • X25

See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What glossary definitions help with understanding FXN?

ataxia ; DNA ; free radicals ; gene ; guanine ; iron ; mitochondria ; mutation ; nucleotide ; pancreas ; protein ; trinucleotide repeat

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Adinolfi S, Trifuoggi M, Politou AS, Martin S, Pastore A. A structural approach to understanding the iron-binding properties of phylogenetically different frataxins. Hum Mol Genet. 2002 Aug 1;11(16):1865-77. (http://www.ncbi.nlm.nih.gov/pubmed/12140189?dopt=Abstract)
  • Castaldo I, Pinelli M, Monticelli A, Acquaviva F, Giacchetti M, Filla A, Sacchetti S, Keller S, Avvedimento VE, Chiariotti L, Cocozza S. DNA methylation in intron 1 of the frataxin gene is related to GAA repeat length and age of onset in Friedreich ataxia patients. J Med Genet. 2008 Dec;45(12):808-12. doi: 10.1136/jmg.2008.058594. Epub 2008 Aug 12. (http://www.ncbi.nlm.nih.gov/pubmed/18697824?dopt=Abstract)
  • Correia AR, Adinolfi S, Pastore A, Gomes CM. Conformational stability of human frataxin and effect of Friedreich's ataxia-related mutations on protein folding. Biochem J. 2006 Sep 15;398(3):605-11. (http://www.ncbi.nlm.nih.gov/pubmed/16787388?dopt=Abstract)
  • OMIM: FRATAXIN (http://omim.org/entry/606829)
  • Gene Review: Friedreich Ataxia (http://www.ncbi.nlm.nih.gov/books/NBK1281)
  • Hebert MD. Targeting the gene in Friedreich ataxia. Biochimie. 2008 Aug;90(8):1131-9. doi: 10.1016/j.biochi.2007.12.005. Epub 2007 Dec 28. Review. (http://www.ncbi.nlm.nih.gov/pubmed/18206656?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/2395)
  • Pandolfo M, Pastore A. The pathogenesis of Friedreich ataxia and the structure and function of frataxin. J Neurol. 2009 Mar;256 Suppl 1:9-17. doi: 10.1007/s00415-009-1003-2. Review. (http://www.ncbi.nlm.nih.gov/pubmed/19283345?dopt=Abstract)
  • Pandolfo M. Friedreich ataxia. Arch Neurol. 2008 Oct;65(10):1296-303. doi: 10.1001/archneur.65.10.1296. Review. (http://www.ncbi.nlm.nih.gov/pubmed/18852343?dopt=Abstract)
  • Seznec H, Simon D, Bouton C, Reutenauer L, Hertzog A, Golik P, Procaccio V, Patel M, Drapier JC, Koenig M, Puccio H. Friedreich ataxia: the oxidative stress paradox. Hum Mol Genet. 2005 Feb 15;14(4):463-74. Epub 2004 Dec 22. (http://www.ncbi.nlm.nih.gov/pubmed/15615771?dopt=Abstract)
  • Stehling O, Elsässer HP, Brückel B, Mühlenhoff U, Lill R. Iron-sulfur protein maturation in human cells: evidence for a function of frataxin. Hum Mol Genet. 2004 Dec 1;13(23):3007-15. Epub 2004 Oct 27. (http://www.ncbi.nlm.nih.gov/pubmed/15509595?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: May 2010
Published: November 24, 2014